Urocortin is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
that in humans is encoded by the ''UCN''
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
. Urocortin belongs to the
corticotropin-releasing factor
Corticotropin-releasing factor family, CRF family is a family of related neuropeptides in vertebrates. This family includes corticotropin-releasing hormone (also known as CRF), urotensin-I, urocortin, and sauvagine. The family can be grouped int ...
(CRF) family of proteins which includes
CRF,
urotensin I,
sauvagine
Sauvagine is a neuropeptide from the corticotropin-releasing factor (CRF) family of peptides and is orthologous to the mammalian hormone, urocortin 1, and the teleost fish hormone, urotensin 1. It is 40 amino acids in length, and has the sequence ...
,
urocortin II
Urocortin 2 (Ucn2) is an endogenous peptide in the corticotrophin-releasing factor (CRF) family.
Urocortin II is a 38-amino acid peptide that is a member of the CRF family of peptides. Unlike Urocortin I, Urocortin II is highly selective for th ...
and
urocortin III
Urocortin III is a 38 amino acid peptide that is a member of the CRF family of peptides. Unlike Urocortin I, and similar to Urocortin II, Urocortin III is highly selective for the CRF2 receptor and does not show affinity for the CRF binding prot ...
. Urocortin is involved in the mammalian stress response, and regulates aspects of appetite and stress response.
Structure, localization, and interactions
Urocortin is a
peptide
Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides.
A ...
composed of 40
amino acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...
s. Urocortin is composed of a single
alpha helix
The alpha helix (α-helix) is a common motif in the secondary structure of proteins and is a right hand-helix conformation in which every backbone N−H group hydrogen bonds to the backbone C=O group of the amino acid located four residues e ...
structure. The human ''UCN'' gene contains two exons, and the entirety of the coding region is contained within the second exon.
Urocortin is expressed widely in the central and peripheral nervous systems, with a pattern similar to that of CRF. Areas of similarity between urocortin and CRF expression include the
supraoptic nucleus
The supraoptic nucleus (SON) is a nucleus of magnocellular neurosecretory cells in the hypothalamus of the mammalian brain. The nucleus is situated at the base of the brain, adjacent to the optic chiasm. In humans, the SON contains about 3,000 n ...
and the
hippocampus
The hippocampus (via Latin from Greek , 'seahorse') is a major component of the brain of humans and other vertebrates. Humans and other mammals have two hippocampi, one in each side of the brain. The hippocampus is part of the limbic system, a ...
.
Urocortin is also expressed in areas distinct from CRF expression; these areas notably include the
median eminence
The median eminence, part of the inferior boundary of the hypothalamus in the brain, is attached to the infundibulum. The median eminence is a small swelling on the tuber cinereum, posterior to and atop the pituitary stalk; it lies in the area rou ...
, the
Edinger-Westphal nucleus, and the sphenoid nucleus.
Additionally, Urocortin is expressed in peripheral tissues such as the heart.
Urocortin is known to interact both with the
CRF type 1 and
CRF type 2 receptors.
Furthermore, Urocortin is thought to be the primary ligand for the CRF type 2 receptor, as it has higher binding affinity for the CRF type 2 receptor than CRF.
Additionally, urocortin interacts with CRF Binding Protein in the mammalian brain.
Stress response and social behavior
Urocortin is closely related to CRF, which mediates the mammalian stress response. Urocortin is consequently implicated in a number of stress responses, primarily relating to appetite and food intake. Administration of urocortin to the central nervous system of mice and rats has been shown to decrease appetite.
Additionally, central urocortin treatment increases anxiety-linked behaviors and increases motor activity in mice and rats.
These general anxiety-linked behaviors are likely induced through the CRF type 1 receptor, and the appetite behaviors are likely induced through the CRF type 2 receptor. The reduction in appetite from urocortin treatment could be a result of suppression of gastric emptying and/or hypoglycemia, which have been shown to result from urocortin treatment. Urocortin expression is stimulated in response to osmotic stress; water deprivation in rats has been shown to induce urocortin expression in the
supraoptic nucleus
The supraoptic nucleus (SON) is a nucleus of magnocellular neurosecretory cells in the hypothalamus of the mammalian brain. The nucleus is situated at the base of the brain, adjacent to the optic chiasm. In humans, the SON contains about 3,000 n ...
.
Montane Voles and
Meadow Voles
The eastern meadow vole (''Microtus pennsylvanicus''), sometimes called the field mouse or meadow mouse, is a North American vole found in eastern Canada and the United States. Its range extends farther south along the Atlantic coast.
The weste ...
are closely related species of voles which are regularly studied as a model for social and mating behavior. The distribution of urocortin-expressing neurons differs in meadow voles compared to montane voles, suggesting urocortin may also play a role in modulating social behavior in some species.
Cardiovascular effects
Urocortin has been shown to induce increases in heart rate and coronary blood flow when applied peripherally.
These effects are likely mediated through the CRF type 2 receptor, as this receptor is found in the
cardiac atria and ventricles. Urocortin also functions to protect cardiovascular tissue from
ischemic
Ischemia or ischaemia is a restriction in blood supply to any tissue, muscle group, or organ of the body, causing a shortage of oxygen that is needed for cellular metabolism (to keep tissue alive). Ischemia is generally caused by problems w ...
injury.
Urocortin's cardiovascular effects separate it from other members of the CRF family, and likely represent its primary biological function.
In non-mammals
Urocortin is not present in all non-mammals; the closet analogue in
teleost
Teleostei (; Greek ''teleios'' "complete" + ''osteon'' "bone"), members of which are known as teleosts ), is, by far, the largest infraclass in the class Actinopterygii, the ray-finned fishes, containing 96% of all extant species of fish. Tel ...
fish is urotensin I.
However, in amphibian species such as ''
Xenopus laevis
The African clawed frog (''Xenopus laevis'', also known as the xenopus, African clawed toad, African claw-toed frog or the ''platanna'') is a species of African aquatic frog of the family Pipidae. Its name is derived from the three short claws ...
'', urocortin is expressed in tissues such as brain, pituitary, kidney, heart, and skin. Urocortin in ''Xenopus'' has been shown to increase
cAMP
Camp may refer to:
Outdoor accommodation and recreation
* Campsite or campground, a recreational outdoor sleeping and eating site
* a temporary settlement for nomads
* Camp, a term used in New England, Northern Ontario and New Brunswick to descri ...
accumulation and inhibit appetite
References
Further reading
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External links
* {{PDBe-KB2, P55089, Urocortin
Corticotropin-releasing hormone receptor agonists
Peptide hormones